Electrostimulation in awake brain mapping is widely used to guide tumor removal, but methodologies can differ substantially across institutions. The authors studied electrostimulation brain mapping data to characterize the variability of the current intensity threshold across patients and the effect of its variations on the number, type, and surface area of the essential language areas detected.

METHODS Over 7 years, the authors prospectively studied 100 adult patients who were undergoing intraoperative brain mapping during resection of left hemisphere tumors. In all 100 cases, the same protocol of electrostimulation brain mapping (a controlled naming task—bipolar stimulation with biphasic square wave pulses of 1-msec duration and 60-Hz trains, maximum train duration 6 sec) and electrocorticography was used to detect essential language areas.

RESULTS The minimum positive thresholds of stimulation varied from patient to patient; the mean minimum intensity required to detect interference was 4.46 mA (range 1.5–9 mA), and in a substantial proportion of sites (13.5%) interference was detected only at intensities above 6 mA. The threshold varied within a given patient for different naming areas in 22% of cases. Stimulation of the same naming area with greater intensities led to slight changes in the type of response in 19% of cases and different types of responses in 4.5%. Naming sites detected were located in subcentimeter cortical areas (50% were less than 20 mm2), but their extent varied with the intensity of stimulation. During a brain mapping session, the same intensity of stimulation reproduced the same type of interference in 94% of the cases. There was no statistically significant difference between the mean stimulation intensities required to produce interfereince in the left inferior frontal lobe (Broca’s area), the supramarginal gyri, and the posterior temporal region.

CONCLUSIONS Intrasubject and intersubject variations of the minimum thresholds of positive naming areas and changes in the type of response and in the size of these areas according to the intensity used may limit the interpretation of data from electrostimulation in awake brain mapping. To optimize the identification of language areas during electrostimulation brain mapping, it is important to use different intensities of stimulation at the maximum possible currents, avoiding afterdischarges. This could refine the clinical results and scientific data derived from these mapping sessions.

Electrocortical stimulation (ECS) is the gold standard for functional brain mapping; however, precise functional mapping is still difficult in patients with language deficits. High gamma activity (HGA) between 80 and 140 Hz on electrocorticography is assumed to reflect localized cortical processing, whereas the cortico-cortical evoked potential (CCEP) can reflect bidirectional responses evoked by monophasic pulse stimuli to the language cortices when there is no patient cooperation. The authors propose the use of “passive” mapping by combining HGA mapping and CCEP recording without active tasks during conscious resections of brain tumors.

Methods Five patients, each with an intraaxial tumor in their dominant hemisphere, underwent conscious resection of their lesion with passive mapping. The authors performed functional localization for the receptive language area, using real-time HGA mapping, by listening passively to linguistic sounds. Furthermore, single electrical pulses were delivered to the identified receptive temporal language area to detect CCEPs in the frontal lobe. All mapping results were validated by ECS, and the sensitivity and specificity were evaluated.

Results Linguistic HGA mapping quickly identified the language area in the temporal lobe. Electrical stimulation by linguistic HGA mapping to the identified temporal receptive language area evoked CCEPs on the frontal lobe. The combination of linguistic HGA and frontal CCEPs needed no patient cooperation or effort. In this small case series, the sensitivity and specificity were 93.8% and 89%, respectively.

Conclusions The described technique allows for simple and quick functional brain mapping with higher sensitivity and specificity than ECS mapping. The authors believe that this could improve the reliability of functional brain mapping and facilitate rational and objective operations. Passive mapping also sheds light on the underlying physiological mechanisms of language in the human brain.

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Warning criteria for monitoring of motor evoked potentials (MEP) after direct cortical stimulation during surgery for supratentorial tumors have been well described. However, little is known about the value of MEP after transcranial electrical stimulation (TES) in predicting postoperative motor deficit when monitoring threshold level. The authors aimed to evaluate the feasibility and value of this method in glioma surgery by using a new approach for interpreting changes in threshold level involving contra- and ipsilateral MEP.

Methods Between November 2013 and December 2014, 93 patients underwent TES-MEP monitoring during resection of gliomas located close to central motor pathways but not involving the primary motor cortex. The MEP were elicited by transcranial repetitive anodal train stimulation. Bilateral MEP were continuously evaluated to assess percentage increase of threshold level (minimum voltage needed to evoke a stable motor response from each of the muscles being monitored) from the baseline set before dural opening. An increase in threshold level on the contralateral side (facial, arm, or leg muscles contralateral to the affected hemisphere) of more than 20% beyond the percentage increase on the ipsilateral side (facial, arm, or leg muscles ipsilateral to the affected hemisphere) was considered a significant alteration. Recorded alterations were subsequently correlated with postoperative neurological deterioration and MRI findings.

Results TES-MEP could be elicited in all patients, including those with recurrent glioma (31 patients) and preoperative paresis (20 patients). Five of 73 patients without preoperative paresis showed a significant increase in threshold level, and all of them developed new paresis postoperatively (transient in 4 patients and permanent in 1 patient). Eight of 20 patients with preoperative paresis showed a significant increase in threshold level, and all of them developed postoperative neurological deterioration (transient in 4 patients and permanent in 4 patients). In 80 patients no significant change in threshold level was detected, and none of them showed postoperative neurological deterioration. The specificity and sensitivity in this series were estimated at 100%. Postoperative MRI revealed gross-total tumor resection in 56 of 82 patients (68%) in whom complete tumor resection was attainable; territorial ischemia was detected in 4 patients.

Conclusions The novel threshold criterion has made TES-MEP a useful method for predicting postoperative motor deficit in patients who undergo glioma surgery, and has been feasible in patients with preoperative paresis as well as in patients with recurrent glioma. Including contra- and ipsilateral changes in threshold level has led to a high sensitivity and specificity.

Diffusion MRI has uniquely enabled in vivo delineation of white matter tracts, which has been applied to the segmentation of eloquent pathways for intraoperative mapping. The last decade has also seen the development from earlier diffusion tensor models to higher-order models, which take advantage of high angular resolution diffusion-weighted imaging (HARDI) techniques. However, these advanced methods have not been widely implemented for routine preoperative and intraoperative mapping. The authors report on the application of residual bootstrap q-ball fiber tracking for routine mapping of potentially functional language pathways, the development of a system for rating tract injury to evaluate the impact on clinically assessed language function, and initial results predicting long-term language deficits following glioma resection.

Methods: The authors have developed methods for the segmentation of 8 putative language pathways including dorsal phonological pathways and ventral semantic streams using residual bootstrap q-ball fiber tracking. Furthermore, they have implemented clinically feasible preoperative acquisition and processing of HARDI data to delineate these pathways for neurosurgical application. They have also developed a rating scale based on the altered fiber tract density to estimate the degree of pathway injury, applying these ratings to a subset of 35 patients with pre- and postoperative fiber tracking. The relationships between specific pathways and clinical language deficits were assessed to determine which pathways are predictive of long-term language deficits following surgery.

Results: This tracking methodology has been routinely implemented for preoperative mapping in patients with brain gliomas who have undergone awake brain tumor resection at the University of California, San Francisco (more than 300 patients to date). In this particular study the authors investigated the white matter structure status and language correlation in a subcohort of 35 subjects both pre- and postsurgery. The rating scales developed for fiber pathway damage were found to be highly reproducible and provided significant correlations with language performance. Preservation of the left arcuate fasciculus (AF) and the temporoparietal component of the superior longitudinal fasciculus (SLF-tp) was consistent in all patients without language deficits (p < 0.001) at the long-term follow-up. Furthermore, in patients with short-term language deficits, the AF and/or SLF-tp were affected, and damage to these 2 pathways was predictive of a long-term language deficit (p = 0.005).

Damage to the motor division of the lower cranial nerves that run into the jugular foramen leads to hoarseness, dysphagia, and the risk of aspiration pneumonia; therefore, its functional preservation during surgical procedures is important. Intraoperative mapping and monitoring of the motor rootlets at the cerebellomedullary cistern using endotracheal tube electrodes is a safe and effective procedure to prevent its injury.

OBJECTIVE: To study the location of the somatic and autonomic motor fibers of the lower cranial nerves related to vocal cord movement.

METHODS: Twenty-four patients with pathologies at the cerebellopontine lesion were studied. General anesthesia was maintained with fentanyl and propofol. A monopolar stimulator was used at amplitudes of 0.05 to 0.1 mA. Both acoustic and visual signals were displayed as vocalis muscle electromyographic activity using endotracheal tube surface electrodes.

RESULTS: The average number of rootlets was 7.4 (range, 5-10); 75% of patients had 7 or 8 rootlets. As many as 6 rootlets (2-4 in most cases) were responsive in each patient. In 23 of the 24 patients, the responding rootlets congregated on the caudal side. The maximum electromyographic response was predominantly in the most caudal or second most caudal rootlet in 79%.

CONCLUSION: The majority of motor fibers of the lower cranial nerves run through the caudal part of the rootlets at the cerebellomedullary cistern, and the maximal electromyographic response was elicited at the most caudal or second most caudal rootlet.

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Neuroanatomy has entered a new era, culminating in the search for the connectome, otherwise known as the brain’s wiring diagram. While this approach has led to landmark discoveries in neuroscience, potential neurosurgical applications and collaborations have been lagging.

In this article, the authors describe the ideas and concepts behind the connectome and its analysis with graph theory. Following this they then describe how to form a connectome using resting state functional MRI data as an example. Next they highlight selected insights into healthy brain function that have been derived from connectome analysis and illustrate how studies into normal development, cognitive function, and the effects of synthetic lesioning can be relevant to neurosurgery.

Finally, they provide a précis of early applications of the connectome and related techniques to traumatic brain injury, functional neurosurgery, and neurooncology.

Methods Operative records, MRI findings, and pathological specimens were evaluated in 12 patients with small deep-seated brain tumor, in which image-guided stereotactic biopsy was performed with the aid of depth microrecording. The tumors were located in the caudate nucleus (1 patient), thalamus (7 patients), midbrain (2 patients), and cortex (2 patients). Surgery was performed with a frameless stereotactic system in 3 patients and with a frame-based stereotactic system in 9 patients. Microrecording was performed to study the electrical activities along the trajectory in the deep brain structures and the tumor. The correlations were studied between the electrophysiological, MRI, and pathological findings. Thirty-two patients with surface or large brain tumor were also studied, in whom image-guided stereotactic biopsy without microrecording was performed.

Results The diagnostic yield in the group with microrecording was 100% (low-grade glioma 4, high-grade glioma 4, diffuse large B-cell lymphoma 3, and germinoma 1), which was comparable to 93.8% in the group without microrecording. The postoperative complication rate was as low as that of the conventional image-guided method without using microelectrode recording, and the mortality rate was 0%, although the target lesions were small and deep-seated in all cases. Depth microrecording revealed disappearance of neural activity in the tumor regardless of the tumor type. Neural activity began to decrease from 6.3 ± 4.5 mm (mean ± SD) above the point of complete disappearance along the trajectory. Burst discharges were observed in 6 of the 12 cases, from 3 ± 1.4 mm above the point of decrease of neural activity. Injury discharges were often found at 0.5–1 mm along the trajectory between the area of decreased and disappeared neural activity. Close correlations between electrophysiological, MRI, and histological findings could be found in some cases.

Conclusions Image-guided stereotactic biopsy performed using depth microrecording was safe, it provided accurate positional information in real time, and it could distinguish the tumor from brain structures during surgery. Moreover, this technique has potential for studying the epileptogenicity of the brain tumor.

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Transient aphasias are often observed in the first few days after a patient has undergone resection in the language- dominant hemisphere. The aims of this prospective study were to characterize the incidence and nature of these aphasias and to determine whether there are relationships between location of the surgical site and deficits in specific language domains.

Methods One hundred ten patients undergoing resection to the language-dominant hemisphere participated in the study. Language was evaluated prior to surgery and 2–3 days and 1 month postsurgery using the Western Aphasia Battery and the Boston Naming Test. Voxel-based lesion-symptom mapping was used to identify relationships between the surgical site location assessed on MRI and deficits in fluency, information content, comprehension, repetition, and naming.

Results Seventy-one percent of patients were classified as aphasic based on the Western Aphasia Battery 2–3 days postsurgery, with deficits observed in each of the language domains examined. Fluency deficits were associated with resection of the precentral gyrus and adjacent inferior frontal cortex. Reduced information content of spoken output was associated with resection of the ventral precentral gyrus and posterior inferior frontal gyrus (pars opercularis). Repetition deficits were associated with resection of the posterior superior temporal gyrus. Naming deficits were associated with resection of the ventral temporal cortex, with midtemporal and posterior temporal damage more predictive of naming deficits than anterior temporal damage. By 1 month postsurgery, nearly all language deficits were resolved, and no language measure except for naming differed significantly from its presurgical level.

Conclusions These findings show that transient aphasias are very common after left hemisphere resective surgery and that the precise nature of the aphasia depends on the specific location of the surgical site. The patient cohort in this study provides a unique window into the neural basis of language because resections are discrete, their locations are not limited by vascular distribution or patterns of neurodegeneration, and language can be studied prior to substantial reorganization.

Resection of a motor eloquent lesion has become safer because of intraoperative neurophysiological monitoring (IOM). Stimulation of subcortical motor evoked potentials (scMEPs) is increasingly used to optimize patient safety. So far, scMEP stimulation has been performed intermittently during resection of eloquently located lesions. Authors of the present study assessed the possibility of using a resection instrument for continuous stimulation of scMEPs.

Methods An ultrasonic surgical aspirator was attached to an IOM stimulator and was used as a monopolar subcortical stimulation probe. The effect of the aspirator’s use at different ultrasound power levels (0%, 25%, 50%, 75%, and 100%) on stimulation intensity was examined in a saline bath. Afterward monopolar stimulation with the surgical aspirator was used during the resection of subcortical lesions in the vicinity of the corticospinal tract in 14 patients in comparison with scMEP stimulation via a standard stimulation electrode. During resection, the stimulation current at which an MEP response was still measurable with subcortical stimulation using the surgical aspirator was compared with the corresponding stimulation current needed using a standard monopolar subcortical stimulation probe at the same location.

Results The use of ultrasound at different energy levels did result in a slight but irrelevant increase in stimulation energy via the tip of the surgical aspirator in the saline bath. Stimulation of scMEPs using the surgical aspirator or monopolar probe was successful and almost identical in all patients. One patient developed a new permanent neurological deficit. Transient new postoperative paresis was observed in 28% (4 of 14) of cases. Gross-total resection was achieved in 64% (9 of 14) cases and subtotal resection (> 80% of tumor mass) in 35% (5 of 14).

Conclusions Continuous motor mapping using subcortical stimulation via a surgical aspirator, in comparison with the sequential use of a standard monopolar stimulation probe, is a feasible and safe method without any disadvantages. Compared with the standard probe, the aspirator offers continuous information on the distance to the corticospinal tract.

Precentral gyrus resections (PGRs) have been regarded as excessively hazardous interventions because of the risk of postoperative major neurological complications.

OBJECTIVE: To evaluate the neurological deterioration that follows PGRs and to assess the topographical risk factors associated with these morbidities.

METHODS: We reviewed 33 consecutive patients who experienced pharmacologically intractable epilepsy and underwent PGR with intraoperative cortical stimulation and mapping while under awake anesthesia. The etiological diagnoses were brain neoplasm in 26 patients (78.8%), cortical lesion in 4 (12.1%), and no lesion in 3 (9.1%). The mean follow-up period was 62.6 months (range, 12-146 months). All topographical analyses of the resected quadrant area were performed based on postoperative magnetic resonance images.

METHODS: Tractography was performed according to both anatomic delineation of the motor cortex (n = 14) and nTMS results (n = 9). After implantation of the definitive electrode, stimulation via the electrode was performed, defining a stimulation threshold for eliciting motor evoked potentials recorded during deep brain stimulation surgery. Others have shown that of arm and leg muscles. This threshold was correlated with the shortest distance between the active electrode contact and both fiber tracks. Results were evaluated by correlation to motor evoked potential monitoring during deep brain stimulation, a surgical procedure causing hardly any brain shift.

RESULTS: Distances to fiber tracks clearly correlated with motor evoked potential thresholds. Tracks based on nTMS had a higher predictive value than tracks based on anatomic motor cortex definition (P < .001 and P = .005, respectively). However, target site, hemisphere, and active electrode contact did not influence this correlation.

CONCLUSION: The implementation of tractography based on nTMS increases the accuracy of fiber tracking. Moreover, this combination of methods has the potential to become a supplemental tool for guiding electrode implantation.

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According to the traditional understanding of cerebrosspinal fluid (CSF) physiology, the majority of CSF is produced by the choroid plexus, circulates through the ventricles, the cisterns, and the subarachnoid space to be absorbed into the blood by the arachnoid villi.

This review surveys key developments leading to the traditional concept. Challenging this concept are novel insights utilizing molecular and cellular biology as well as neuroimaging, which indicate that CSF physiology may be much more complex than previously believed. The CSF circulation comprises not only a directed flow of CSF, but in addition a pulsatile to and fro movement throughout the entire brain with local fluid exchange between blood, interstitial fluid, and CSF. Astrocytes, aquaporins, and other membrane transporters are key elements in brain water and CSF homeostasis. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates, which exceed the choroidal CSF production rate by far. The CSF circulation around blood vessels penetrating from the subarachnoid space into the Virchow Robin spaces provides both a drainage pathway for the clearance of waste molecules from the brain and a site for the interaction of the systemic immune system with that of the brain. Important physiological functions, for example the regeneration of the brain during sleep, may depend on CSF circulation.

The emerging field of neuroprosthetics is focused on the development of new therapeutic interventions that will be able to restore some lost neural function by selective electrical stimulation or by harnessing activity recorded from populations of neurons.

As more and more patients benefit from these approaches, the interest in neural interfaces has grown significantly and a new generation of penetrating microelectrode arrays are providing unprecedented access to the neurons of the central nervous system (CNS). These microelectrodes have active tip dimensions that are similar in size to neurons and because they penetrate the nervous system, they provide selective access to these cells (within a few microns).

However, the very long-term viability of chronically implanted microelectrodes and the capability of recording the same spiking activity over long time periods still remain to be established and confirmed in human studies.

Here we review the main responses to acute implantation of microelectrode arrays, and emphasize that it will become essential to control the neural tissue damage induced by these intracortical microelectrodes in order to achieve the high clinical potentials accompanying this technology.

Until now there has been no reliable stimulation protocol for inducing transient language disruptions while mapping Broca’s area. Despite the promising data of only a few studies in which speech arrest and language disturbances have been induced, certain concerns have been raised. The purpose of this study was to map Broca’s area by using event-related navigated transcranial magnetic stimulation (nTMS) to generate a modified patterned nTMS protocol.

Methods. Eleven right-handed subjects underwent nTMS to Broca’s area while engaged in a visual object-naming task. Navigated TMS was triggered 300 msec after picture presentation. The modified patterned nTMS protocol consists of 4 stimuli with an interstimulus interval of 6 msec; 8 or 16 of those bursts were repeated with a burst repetition rate of 12 Hz. Prior to mapping of Broca’s area, the primary motor cortices (M1) for hand and laryngeal muscles were mapped. The Euclidian distance on MRI was measured between cortical points eliciting transient language disruptions and M1 for the laryngeal muscle.

Conclusions. The stimulation paradigm with the modified patterned nTMS protocol was shown to be promising and might gain more widespread use in speech localization in clinical and research applications.

The authors developed a new mapping technique to overcome the temporal and spatial limitations of classic subcortical mapping of the corticospinal tract (CST). The feasibility and safety of continuous (0.4–2 Hz) and dynamic (at the site of and synchronized with tissue resection) subcortical motor mapping was evaluated.

Methods. The authors prospectively studied 69 patients who underwent tumor surgery adjacent to the CST (< 1 cm using diffusion tensor imaging and fiber tracking) with simultaneous subcortical monopolar motor mapping (short train, interstimulus interval 4 msec, pulse duration 500 μsec) and a new acoustic motor evoked potential alarm. Continuous (temporal coverage) and dynamic (spatial coverage) mapping was technically realized by integrating the mapping probe at the tip of a new suction device, with the concept that this device will be in contact with the tissue where the resection is performed. Motor function was assessed 1 day after surgery, at discharge, and at 3 months.

Conclusions. Continuous dynamic mapping was found to be a feasible and ergonomic technique for localizing the exact site of the CST and distance to the motor fibers. The acoustic feedback and the ability to stimulate the tissue continuously and exactly at the site of tissue removal improves the accuracy of mapping, especially at low (< 5 mA) stimulation intensities. This new technique may increase the safety of motor eloquent tumor surgery.

Resection of abnormal brain tissue lying near the sensorimotor cortex entails precise localization of the central sulcus. Mapping of this area is achieved by applying invasive direct cortical electrical stimulation. However, noninvasive methods, particularly functional magnetic resonance imaging (fMRI), are also used. As a supplement to fMRI, localization of somatosensory-evoked potentials (SEPs) recorded with an electroencephalogram (EEG) has been proposed, but has not found its place in clinical practice.

METHODS: We applied electrical source imaging in 49 subjects, recorded with highdensity EEG (256 channels). We compared it with fMRI in 18 participants and with direct cortical electrical stimulation in 6 epileptic patients.

RESULTS: Comparison of SEP source imaging with fMRI indicated differences of 3 to 8 mm, with the exception of the mesial-distal orientation, where variances of up to 20 mm were found. This discrepancy is explained by the fact that the source maximum of the first SEP peak is localized deep in the central sulcus (area 3b), where information initially arrives. Conversely, fMRI showed maximal signal change on the lateral surface of the postcentral gyrus (area 1), where sensory information is integrated later in time. Electrical source imaging and fMRI showed mean Euclidean distances of 13 and 14 mm, respectively, from the contacts where electrocorticography elicited sensory phenomena of the contralateral upper limb.

CONCLUSION: SEP source imaging, based on high-density EEG, reliably identifies the depth of the central sulcus. Moreover, it is a simple, flexible, and relatively inexpensive alternative to fMRI.

Safe resection of intramedullary spinal cord tumors can be challenging, because they often alter the cord anatomy. Identification of neurophysiologically viable dorsal columns (DCs) and of neurophysiologically inert tissue, eg, median raphe (MR), as a safe incision site is crucial for avoiding postoperative neurological deficits. We present our experience with and improvements made to our previously described technique of DC mapping, successfully applied in a series of 12 cases.

OBJECTIVE: To describe a new, safe, and reliable technique for intraoperative DC mapping.

METHODS: The right and left DCs were stimulated by using a bipolar electric stimulator and the triggered somatosensory evoked potentials recorded from the scalp. Phase reversal and amplitude changes of somatosensory evoked potentials were used to neurophysiologically identify the laterality of DCs, the inert MR, as well as other safe incision sites.

RESULTS: The MR location was neurophysiologically confirmed in all patients in whom this structure was first visually identified as well as in those in whom it was not, with 1 exception. DCs were identified in all patients, regardless of whether they could be visually identified. In 3 cases, negative mapping with the use of this method enabled the surgeon to reliably identify additional inert tissue for incision. None of the patients had postoperative worsening of the DC function.

CONCLUSION: Our revised technique is safe and reliable, and it can be easily incorporated into routine intramedullary spinal cord tumor resection. It provides crucial information to the neurosurgeon to prevent postoperative neurological deficits.